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Войти в исследования Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
Higher TIGIT expression in the intraperitoneal immune microenvironment is associated with shorter progression-free survival in patients with gastric cancer with peritoneal metastasis treated with intraperitoneal paclitaxel.
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Yamada Atsushi, Imano Motohiro, Kato Hiroaki, Kobayashi Ryusuke, Kounami Naoko, Terada Masuhiro, Kohda Masashi, Nakanishi Tomoya, Hiraki Yoko, Shiraishi Osamu, Yasuda Atsushi, Shinkai Masayuki, Yasuda Takushi
Аннотация
PURPOSE: Gastric cancer with peritoneal metastasis has a poor prognosis. This exploratory study evaluated whether immune checkpoint molecules in the intraperitoneal immune microenvironment are associated with clinical outcomes during intraperitoneal paclitaxel (ipPTX)-based combination chemotherapy.
METHODS: Twenty-nine previously untreated patients with gastric cancer and macroscopic peritoneal metastasis who underwent staging laparoscopy and received ipPTX-based combination chemotherapy were retrospectively analyzed. Lymphocyte subsets in peritoneal lavage fluid were evaluated by flow cytometry. TIGIT, TIM-3, and LAG-3 expression was assessed in cell block specimens prepared from peritoneal lavage fluid by immunohistochemistry. Biomarker analyses were exploratory. Immune-related markers were analyzed primarily as continuous variables, and multivariable progression-free survival (PFS) and overall survival (OS) models were restricted to TIGIT and baseline Peritoneal Carcinomatosis Index (PCI) using Firth's penalized Cox regression.
RESULTS: Median PFS and OS were 10.6 and 17.2 months, respectively. Among 27 patients evaluable for TIGIT, higher TIGIT expression was associated with shorter PFS in a continuous-variable Cox model (hazard ratio [HR] per 10-percentage-point increase, 1.53; 95% confidence interval [CI] 1.12-2.08; p = 0.008). After adjustment for baseline PCI, the association remained (HR, 1.48; 95% CI 1.04-2.10; p =0.030). TIM-3 did not show a clear association with survival outcomes.
CONCLUSIONS: Higher TIGIT expression in the intraperitoneal immune microenvironment was associated with shorter PFS in this small exploratory cohort receiving ipPTX-based combination chemotherapy.
METHODS: Twenty-nine previously untreated patients with gastric cancer and macroscopic peritoneal metastasis who underwent staging laparoscopy and received ipPTX-based combination chemotherapy were retrospectively analyzed. Lymphocyte subsets in peritoneal lavage fluid were evaluated by flow cytometry. TIGIT, TIM-3, and LAG-3 expression was assessed in cell block specimens prepared from peritoneal lavage fluid by immunohistochemistry. Biomarker analyses were exploratory. Immune-related markers were analyzed primarily as continuous variables, and multivariable progression-free survival (PFS) and overall survival (OS) models were restricted to TIGIT and baseline Peritoneal Carcinomatosis Index (PCI) using Firth's penalized Cox regression.
RESULTS: Median PFS and OS were 10.6 and 17.2 months, respectively. Among 27 patients evaluable for TIGIT, higher TIGIT expression was associated with shorter PFS in a continuous-variable Cox model (hazard ratio [HR] per 10-percentage-point increase, 1.53; 95% confidence interval [CI] 1.12-2.08; p = 0.008). After adjustment for baseline PCI, the association remained (HR, 1.48; 95% CI 1.04-2.10; p =0.030). TIM-3 did not show a clear association with survival outcomes.
CONCLUSIONS: Higher TIGIT expression in the intraperitoneal immune microenvironment was associated with shorter PFS in this small exploratory cohort receiving ipPTX-based combination chemotherapy.